Production method of amine compounds by the reaction of ammonia or a primary or secondary amine compound and a carbonyl compound is known as reductive amination reaction, which is one of the standard methods for producing amine compounds. As methods for producing amine compounds by reductive amination reaction known from the prior art, following methods are known: 1) a method by hydrogenation reaction using solid catalyst such as Raney Ni, Raney Co, Pt/activated carbon and Pd/activated carbon as heterogeneous catalyst, 2) a method using boron-based reactant such as NaBH3CN and NaBH(OAc)3 as hydride reducing agent, and 3) a method using metal complex catalyst as homogeneous catalyst.
A method of 1) is described in, for example, J. Am. Chem. Soc. 1941, 63, 749 (Non-patent Document 1) and J. Org. Chem. 1962, 27, 2205 (Non-Patent Document 2).
As a method of 2), the following methods are known: a) a method using NaBH3CN described in J. Am. Chem. Soc. 1971, 93, 2897 (Non-Patent Document 3), b) a method using NaBH(OAc)3 described in J. Org. Chem. 1996, 61, 3849 (non-patent document 4), c) a method using pyridine borane described in J. Org. Chem. 1995, 60, 5995 (Non-Patent Document 5), d) a method using 2-picoline borane described in JP A 2004-256511 (Patent Document 1), and e) a method using 5-ethyl-2-methylpyridine borane described in Tetrahedron Letters 2008, 49, 5152-5155 (non-Patent Document 6).
As a method of 3), the following methods are known: a production method to obtain primary amines by reacting carbonyl compound, ammonia, and hydrogen under the presence of hydrogenation catalyst, described in JP No. 4059978 (Patent Document 2); a method by hydrogenation reaction using rhodium complex having phosphine ligand, described in Chem. Comm., 2000, 1867-1868 (Non-Patent Document 7); a method by hydrogenation reaction using a combination of [Rh(cod)Cl2]2 complex and TPPTS ligand described in Org. Lett. 2002, 4, 2055-2058 (Non-Patent Document 8); a method using [Cp*RhCl2]2 as complex catalyst, ammonium formate as amine source and hydrogen source, described in J. Org. Chem. 2002, 67 8685-8687 (Non-Patent Document 9); and a method by reductive hydride-transfer amination of carbonyl compound and amine compound under the presence of hydrogen donor as reducing agent and transition metal complex catalyst containing at least one metal selected from the group consisting of Ru, Rh and Ir, described in JP A 2004-537588 (Patent Document 3).
However, production methods by hydrogenation reaction using solid catalyst have a problem in terms of safety and reaction operability because the methods require a pressure-resistant reactor for hydrogen gas used as hydrogen source, and a problem of not applicable to substrates having carbon-carbon multiple binding sites and hydrogenation-susceptible functional groups such as cyano group and nitro group. Since boron-based reactants do not require a pressure-resistant reactor, the methods using them are superior in operability; however, they are inferior in terms of economic and environmental aspects because the reaction is not a catalytic reaction, and the following problems also exist in each reactant.
Regarding the method using NaBH3CN, industrial use is difficult because of its toxicity. In the method using NaBH(OAc)3, there is a restriction of solvent to be used due to its solubility, and the use of an excess amount is required because NaBH(OAc)3 has only one hydride source in the molecule. Regarding the method using pyridine borane, there are problems that the storage stability of the reagent itself is poor, and the reagent decomposes at 54° C. or higher. In the method using 2-picoline borane, although the stability of the reactant 2-picoline borane is higher than that of pyridine borane, it has a handling problem because its melting point is 44-45° C. 5-Ethyl-2-methylpyridine borane has a problem, similar to the above two pyridine-borane-based reactants, that the removal of the reactant from reaction solution is not easy.
As an example of using a homogeneous catalyst, in the method described in JP No. 4059978, a pressure-resistant reactor is required because hydrogen is used as a hydrogen source, and its industrial implementation is problematic from the standpoint of safety and reaction operability because reaction is carried out at high temperature (150° C.) and high pressure (50 atm or more) conditions. The method described in Chem. Comm., 2000, 1867-1868 is a reaction under high pressure (50 atm), and alcohol by-products are produced and the selectivity of amine is poor, so that the method will not be an efficient production method of amine compounds. The hydrogenation reaction by combination of [Rh(cod)Cl]2 complex and TPPTS ligand, described in J. Org. Lett. 2002, 4, 2055-2058, is performed at high temperature and high pressure conditions, so that its industrial implementation is problematic from the standpoint of safety and reaction operability.
As shown in J. Org. Chem. 2002, 67, 8685-8687, in the method using a [Cp*RhCl2]2 complex, i.e., organometallic complex, as an catalyst, solid ammonium formate is used as a hydrogen source and an amine source; therefore it is an excellent method in terms of reaction operability and safety, whereas its industrial use is problematic because catalytic activity is low. The method described in JP A 2004-537588 exhibits very poor reaction efficiency, i.e., a ratio of [substrate/catalyst] of approximately 50-100, and in some cases alcohol by-products are generated and reaction does not complete; thus, its industrial implementation is difficult.
A method for obtaining optically active amine by diastereoselective reductive amination reaction using optically active amine as an amine source is also known. In Adv. Synth. Catal. 2010, 352, 753-819 (Non-Patent Document 10), the following method is described: optically active α-methylbenzylamine is used as an amine source, and under the co-presence of Lewis acid such as Ti(O-i-Pr)4 and Yb(OAc)3, using a solid catalyst such as Raney Ni, Pd/C or Pt/C, a highly diastereoselective reductive amination reaction is carried out under hydrogenation conditions to obtain optically active amine by the deprotection of protecting groups. In addition, in the same document a method of diastereoselective reductive amination reaction, using optically active tert-butyl sulfinamide as the amine source, under the presence of Ti(OEt)4 and using DIBAL at a reaction temperature of −48° C. or using L-selectride, is described.
However, since the former method requires an equimolar or more of Lewis acid relative to the substrate, and the amount of solid catalyst used is large; therefore, the production cost is high, and post-treatment after the reaction is complicated; thus, its industrial implementation is problematic from the viewpoint of reaction operability and safety. In the latter reaction, under cryogenic conditions of −48° C., 2 equivalents of Lewis acid relative to the substrate and expensive amine are required; therefore, from the viewpoint of reaction operability, safety and economical aspect, the method cannot be a practical production method similar to the former method.
In JP A 2010-235604 (Patent Document 4) and JP A 2012-062270 (Patent Document 5), a reductive amination reaction using formic acid or ammonium formate as a hydrogen source is described.